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Article

Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

1
Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy
2
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy
3
Medical Oncology, Azienda ULSS 2, 31100 Treviso, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(1), 66; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010066
Received: 16 October 2019 / Revised: 11 December 2019 / Accepted: 16 December 2019 / Published: 20 December 2019
(This article belongs to the Collection Feature Papers in Molecular Oncology)
Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays. View Full-Text
Keywords: non-small-cell lung cancer (NSCLC); liquid biopsy; loss of heterozygosity (LOH); cell-free DNA (cfDNA); epidermal growth factor receptor (EGFR); Kirsten rat sarcoma homologous (KRAS) non-small-cell lung cancer (NSCLC); liquid biopsy; loss of heterozygosity (LOH); cell-free DNA (cfDNA); epidermal growth factor receptor (EGFR); Kirsten rat sarcoma homologous (KRAS)
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MDPI and ACS Style

Boldrin, E.; Nardo, G.; Zulato, E.; Bonanno, L.; Polo, V.; Frega, S.; Pavan, A.; Indraccolo, S.; Saggioro, D. Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients. Int. J. Mol. Sci. 2020, 21, 66. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010066

AMA Style

Boldrin E, Nardo G, Zulato E, Bonanno L, Polo V, Frega S, Pavan A, Indraccolo S, Saggioro D. Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients. International Journal of Molecular Sciences. 2020; 21(1):66. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010066

Chicago/Turabian Style

Boldrin, Elisa, Giorgia Nardo, Elisabetta Zulato, Laura Bonanno, Valentina Polo, Stefano Frega, Alberto Pavan, Stefano Indraccolo, and Daniela Saggioro. 2020. "Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients" International Journal of Molecular Sciences 21, no. 1: 66. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010066

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